The exact role of endotoxemia in human septic shock remains controversial. Definition of the importance, time course, and level of endotoxemia in human septic shock has become imperative with the development of a number of investigational therapies aimed at inhibiting or neutralizing endotoxin. In this investigation we are prospectively studying endotoxemia in hemodynamically monitored patients with septic shock. Frequent, serial endotoxin determinations are followed using a highly sensitive chromogenic limulus amebocyte lysate assay. Preliminary results have shown that endotoxemia is frequent (43%) but intermittent and correlates with the development of severe shock and multiple organ failure. These studies should help define the role played by endotoxin in the septic shock syndrome and allow for the more rational design of studies evaluating the therapeutic efficacy of anti-endotoxin agents. The first manuscript from the project has recently been accepted for publication by Chest. The investigation is continuing to prospectively examine the relationship between endotoxemia and the release various endogenous cytokines (TNF, IL-1, IL-6, IL-8).